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The association between fluoroquinolones and aortic dissection and aortic aneurysms: a systematic review and meta-analysis.

ABSTRACT: Previous studies have drawn causal associations between fluoroquinolone use and collagen pathologies including tendon rupture and retinopathy. This meta-analysisattempted to assess the association between fluoroquinolone use and the risk of aortic dissection or aortic aneurysm. A systematic search was performed on Medline, EMBASE, and the Cochrane library. 9 studies were included in final analysis. Primary random-effects meta-analysis of 7 studies, excluding 2 pharmacovigilance studies demonstrated statistically increased odds of aortic dissection (OR, 2.38; 95% CI, 1.71-3.32) aortic aneurysm (OR, 1.98; 95% CI, 1.59-2.48), and aortic aneurysm or dissection (OR, 1.47; 95% CI, 1.13-1.89; I² = 72%) with current use of fluoroquinolones compared to their nonuser counterparts. Based on the "number needed-to-harm" analysis, 7246 (95% CI: 4329 to 14,085) patients would need to be treated with fluoroquinolones for a duration of at least three days in order for one additional patient to be harmed, assuming a population baseline incidence of aortic dissection and aneurysm rupture to be 10 per 100,000 patient-years. With strong statistical association, these findings suggest a causal relationship, warranting future research to elucidate the pathophysiological and mechanistic plausibility of this association. These findings however, should not cease prescription of fluoroquinolones, especially when clinically indicated.

SUBMITTER: Wee I

PROVIDER: S-EPMC8154986 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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The association between fluoroquinolones and aortic dissection and aortic aneurysms: a systematic review and meta-analysis.

Wee Ian I Chin Brian B Syn Nicholas N Lee Keng Siang KS Ng Jun Jie JJ Choong Andrew M T L AMTL

Scientific reports 20210526 1

Previous studies have drawn causal associations between fluoroquinolone use and collagen pathologies including tendon rupture and retinopathy. This meta-analysisattempted to assess the association between fluoroquinolone use and the risk of aortic dissection or aortic aneurysm. A systematic search was performed on Medline, EMBASE, and the Cochrane library. 9 studies were included in final analysis. Primary random-effects meta-analysis of 7 studies, excluding 2 pharmacovigilance studies demonstra ...[more]

PMID: 34040146

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Project description:ImportancePrevious observational studies have suggested that fluoroquinolones are associated with aortic aneurysm or dissection, but these studies may be subject to confounding by indication or surveillance bias.ObjectiveTo assess the association of fluoroquinolones with risk of aortic aneurysm or aortic dissection (AA/AD) while accounting for potential confounding by fluoroquinolone indication and bias owing to differential surveillance.Design, setting, and participantsIn an observational cohort study using a US commercial claims database, 2 pairwise 1:1 propensity score-matched cohorts were identified: patients aged 50 years or older with a diagnosis of pneumonia 3 days or less before initiating treatment with a fluoroquinolone or azithromycin and patients aged 50 years or older with a urinary tract infection (UTI) diagnosis 3 days or less before initiating a fluoroquinolone or combined trimethoprim and sulfamethoxazole. Hazard ratios (HRs) and 95% CIs were estimated controlling for 85 baseline confounders. In a secondary analysis, patients receiving fluoroquinolones were compared with those receiving amoxicillin, both with and without considering baseline aortic imaging, to address differences in detection of AA/AD before antibiotic use. Data on patients within the database from January 1, 2003, through September 30, 2015, were analyzed. Data analysis was conducted from July 23, 2019, to July 6, 2020.Main outcomes and measuresHospitalization for AA/AD occurring within 60 days following treatment initiation.ResultsAfter propensity score matching, patient characteristics were well balanced, with 279 554 patients (mean [SD] age, 63.66 [10.93] years; 149 976 women [53.6%]) in the pneumonia cohort and 948 364 patients (mean [SD] age, 62.06 [10.33] years; 823 667 women [86.9%]) in the UTI cohort. Initiators of fluoroquinolones (n = 139 772 pairs in the pneumonia cohort and n = 474 182 pairs in the UTI cohort) had an increased rate of AA/AD compared with initiators of azithromycin (HR, 2.57; 95% CI, 1.36-4.86; incidence, 0.03% for fluoroquinolones vs 0.01% for azithromycin) but no increased rate compared with initiators of combined trimethoprim and sulfamethoxazole (HR, 0.99; 95% CI, 0.62-1.57; incidence, <0.01% in both UTI groups). Secondary analysis using amoxicillin as a comparator (n = 3 976 162 pairs) produced results consistent with those from earlier studies (HR, 1.54; 95% CI, 1.33-1.79; incidence, <0.01% in both groups). Requiring baseline imaging in this cohort (n = 542 649 pairs) to address surveillance bias attenuated the increased rate (HR, 1.13; 95% CI, 0.96-1.33; incidence, 0.06% for fluoroquinolones vs 0.05% for amoxicillin).Conclusions and relevanceThe findings of this nationwide cohort study of adults with pneumonia or UTI suggest an increased relative rate of AA/AD associated with fluoroquinolones within the pneumonia cohort but not within the UTI cohort. In both cohorts, the absolute rate of AA/AD appeared to be low (<0.1%). The increased relative rate observed in the pneumonia cohort may be due to residual confounding or surveillance bias.

Project description:ObjectiveThere is no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. This systematic review aimed to summarise available trial evidence on the efficacy of pharmacotherapy in limiting AAA growth and AAA-related events.MethodsA systematic literature search was performed to examine the efficacy of pharmacotherapy in reducing AAA growth and AAA-related events. Pubmed, Embase (Excerpta Medica Database), and the Cochrane library were searched from March, 1999 to March 29, 2022. AAA growth (mm/year) in the intervention and control groups was expressed as mean and standard deviation (SD). The results of AAA growth were expressed as mean difference (MD) and its 95% confidence interval (95% CI). Odds ratios (ORs) were calculated for the AAA-related events.Heterogeneity was quantified using the I2 statistic. Forest plots were created to show the pooled results of each outcome.OutcomesA total of 1373 articles were found in different databases according to the search strategy, and 10 articles were identified by hand searching. A total of 26 articles were included in our systematic review after the screening. For the studies of metformin, the meta-analysis demonstrated that metformin use was associated with a lower AAA growth rate (MD: -0.81 mm/y, 95% CI: -1.19 to -0.42, P < 0.0001, I2 = 87%), Metformin use also was related to the lower rates of AAA-related events (OR: 0.53, 95% CI: 0.36 to 0.76, P = 0.0007, I2 = 60%). The hypotensive drugs of the studies mainly included angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARB), and propranolol. The overall meta-analysis of blood pressure-lowering drugs reported no significant effect in limiting the AAA growth (MD: 0.31mm/year, 95%CI: -0.03 to 0.65, P = 0.07, I2 = 66%) and AAA-related events (OR: 1.33, 95%CI: 0.76 to 2.32, P = 0.32, I2 = 98%), In the subgroup analysis of the hypotensive drugs, the ACEI/ARB and propranolol also showed no significant in reducing the AAA growth and AAA-related events. The meta-analysis of the antibiotics demonstrated that the antibiotics were not associated with a lower AAA growth rate (MD: -0.27 mm/y, 95% CI: -0.88 to 0.34, P = 0.39, I2 = 77%) and AAA-related events (OR: 0.94, 95%CI: 0.65 to 1.35, P = 0.72, I2 = 0%). The results of statins also showed no significant effect in limiting AAA growth (MD: -1.11mm/year, 95%CI: -2.38 to 0.16, P = 0.09, I2 = 96%) and AAA-related events (OR: 0.53, 95%CI: 0.26 to 1.06, P = 0.07, I2 = 92%).ConclusionIn conclusion, effective pharmacotherapy for AAA was still lacking. Although the meta-analysis showed that metformin use was associated with lower AAA growth and AAA-related events, all of the included studies about metformin were cohort studies or case-control studies. More randomized controlled trials (RCTs) are needed for further verification.

Dataset Information

The association between fluoroquinolones and aortic dissection and aortic aneurysms: a systematic review and meta-analysis.

Publications

The association between fluoroquinolones and aortic dissection and aortic aneurysms: a systematic review and meta-analysis.

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